Linking membrane architecture to function by correlative microscopy
Eukaryotic cells use membranes to organize their numerous intracellular processes. These membranes are not just inert barriers. They are compositionally and morphologically dynamic, and their shape and topology are intimately tied to organelle function. Essential processes such as endocytosis, intracellular transport, and communication at organelle contact sites are all dependent on properly regulating membrane architecture. Conversely, defects in membrane morphology of different organelles have been linked to various human diseases. Yet the mechanisms that couple membrane architecture to associated cellular functions are poorly understood.
Our current interests focus on membrane dynamics controlling cargo traffic through the network of endosomes, and the role of membrane architecture at contact sites between two organelles. Endosomal sorting is critical for signalling and nutrient uptake, as well as for regulating the composition of the plasma membrane, but it is also hijacked by pathogens for cell entry. Organelle contact sites are important for communication and exchange of molecules such as lipids and calcium.
We address these topics using correlative light and electron microscopy to combine information on protein composition and dynamics with 3D membrane ultrastructure. By complementing microscopy with molecular genetics, we seek to provide a mechanistic understanding of how membrane architecture intersects with cellular processes involving inter-membrane communication and transport.
- Kukulski. W., Picco, A., Specht, T., Briggs, J.A., Kaksonen, M. (2016)
Clathrin modulates vesicle scission, but not invagination shape, in yeast endocytosis.
Elife 5: pii: e16036.
- Kukulski, W., Schorb, M., Kaksonen, M., and Briggs, J.A. (2012). (2012)
Plasma membrane reshaping during endocytosis is revealed by time-resolved electron tomography.
Cell 150: 508-520.
- Kukulski, W., Schorb, M., Welsch, S., Picco, A., Kaksonen, M., and Briggs, J.A. (2011)
Correlated fluorescence and 3D electron microscopy with high sensitivity and spatial precision.
J. Cell Biol. 192: 111-119.
- Patrick Hoffmann
- Iva Ganeva
- Michael Wozny
- Alicia Borgeaud